title: Association between circulating endostatin, hypertension duration, and hypertensive target-organ damage.
abstract: Our aim is to study associations between circulating endostatin, hypertension duration, and hypertensive target-organ damage. Long-term hypertension induces cardiovascular and renal remodeling. Circulating endostatin, a biologically active derivate of collagen XVIII, has been suggested to be a relevant marker for extracellular matrix turnover and remodeling in various diseases. However, the role of endostatin in hypertension and hypertensive target-organ damage is unclear. Serum endostatin was measured in 2 independent community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 51%; n = 812; mean age, 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=785; mean age, 77.6 years). Retrospective data on blood pressure measurements and antihypertensive medication (PIVUS >5 years, ULSAM >27 years), and cross-sectional data on echocardiographic left ventricular mass, endothelial function (endothelium-dependent vasodilation assessed by the invasive forearm model), and urinary albumin/creatinine ratio were available. In PIVUS, participants with ≥ 5 years of history of hypertension portrayed 0.42 SD (95% confidence interval, 0.23-0.61; P<0.001) higher serum endostatin, compared with that of normotensives. This association was replicated in ULSAM, in which participants with 27 years hypertension duration had the highest endostatin (0.57 SD higher; 95% confidence interval, 0.35-0.80; P<0.001). In addition, higher endostatin was associated with higher left ventricular mass, worsened endothelial function, and higher urinary albumin/creatinine ratio (P<0.03 for all) in participants with prevalent hypertension. Circulating endostatin is associated with the duration of hypertension, and vascular, myocardial, and renal indices of hypertensive target-organ damage. Further studies are warranted to assess the prognostic role of endostatin in individuals with hypertension.
authors.affiliation: Centre for Family Medicine, Alfred Nobels Allé 12, 141 83 Huddinge, Sweden. axelcefam@hotmail.com; or Johan Ärnlöv, Department of Public Health and Caring Sciences/Geriatrics, Uppsala Science Park, SE-75185 Uppsala, Sweden. E-mail johan.arnlov@pubcare.uu.se.
authors.forename: Axel C
authors.initials: AC
authors.lastname: Carlsson
authors.forename: Toralph
authors.initials: T
authors.lastname: Ruge
authors.forename: Johan
authors.initials: J
authors.lastname: Sundström
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.forename: Johan
authors.initials: J
authors.lastname: Arnlöv
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000502:physiology*; D043169:Endostatins / Q000097:blood*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies
chemical_list: D000959:Antihypertensive Agents; D043169:Endostatins
keywords: Sweden; angiogenesis effects; antiangiogenesis effects; cohort study; endothelial cells; epidemiology; extracellular matrix; vascular stiffness